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Protein

Toll-like receptor 4

Gene

Tlr4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) (PubMed:9851930, PubMed:9989976, PubMed:20133493). Acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:24380872). Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate. In complex with TLR6, promotes sterile inflammation in monocytes/macrophages in response to oxidized low-density lipoprotein (oxLDL) or amyloid-beta 42. In this context, the initial signal is provided by oxLDL- or amyloid-beta 42-binding to CD36. This event induces the formation of a heterodimer of TLR4 and TLR6, which is rapidly internalized and triggers inflammatory response, leading to the NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway, as well as IL1B secretion. Binds electronegative LDL (LDL-) and mediates the cytokine release induced by LDL- (By similarity).By similarity8 Publications

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionReceptor
Biological processImmunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-MMU-140534 Caspase activation via Death Receptors in the presence of ligand
R-MMU-166016 Toll Like Receptor 4 (TLR4) Cascade
R-MMU-166166 MyD88-independent TLR4 cascade
R-MMU-2562578 TRIF-mediated programmed cell death
R-MMU-5686938 Regulation of TLR by endogenous ligand
R-MMU-936964 Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
R-MMU-937041 IKK complex recruitment mediated by RIP1
R-MMU-937072 TRAF6-mediated induction of TAK1 complex within TLR4 complex

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Toll-like receptor 4
Alternative name(s):
CD_antigen: CD284
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:Tlr4
Synonyms:Lps
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiMus musculus (Mouse)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri10090 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000000589 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 4

Organism-specific databases

Mouse genome database (MGD) from Mouse Genome Informatics (MGI)

More...
MGIi
MGI:96824 Tlr4

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini26 – 638ExtracellularSequence analysisAdd BLAST613
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei639 – 659HelicalSequence analysisAdd BLAST21
Topological domaini660 – 835CytoplasmicSequence analysisAdd BLAST176

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

The protein is encoded by the Lps locus, an important susceptibility locus, influencing the propensity to develop a disseminated Gram-negative infection.2 Publications

<p>This subsection of the ‘Pathology and Biotech’ section describes the in vivo effects caused by ablation of the gene (or one or more transcripts) coding for the protein described in the entry. This includes gene knockout and knockdown, provided experiments have been performed in the context of a whole organism or a specific tissue, and not at the single-cell level.<p><a href='/help/disruption_phenotype' target='_top'>More...</a></p>Disruption phenotypei

Animals with a double knockout of APOE and TLR4, fed a Western diet for 12 weeks, have less aortic plaque formation than single APOE knockout mice. They also show lower serum concentrations of IL1A, ILB and IL18.1 Publication

Keywords - Diseasei

Disease mutation

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...
ChEMBLi
CHEMBL1795167

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 25Sequence analysisAdd BLAST25
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000003472326 – 835Toll-like receptor 4Add BLAST810

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi28 ↔ 391 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi34N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi75N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi172N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi204N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi237N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi280 ↔ 3041 Publication
Glycosylationi307N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi388 ↔ 3891 Publication
Glycosylationi492N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi495N-linked (GlcNAc...) asparagine1
Glycosylationi524N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi572N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi575N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi580 ↔ 6061 Publication
Disulfide bondi582 ↔ 6251 Publication
Glycosylationi613N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi621N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi622N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQB - The MaxQuant DataBase

More...
MaxQBi
Q9QUK6

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
Q9QUK6

PRoteomics IDEntifications database

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PRIDEi
Q9QUK6

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
Q9QUK6

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
Q9QUK6

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Highly expressed in heart, spleen, lung and muscle. Lower levels are found in liver and kidney. Expressed in macrophages.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSMUSG00000039005 Expressed in 161 organ(s), highest expression level in aortic valve

CleanEx database of gene expression profiles

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CleanExi
MM_TLR4

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
Q9QUK6 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...
Genevisiblei
Q9QUK6 MM

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Belongs to the lipopolysaccharide (LPS) receptor, a multi-protein complex containing at least CD14, LY96 and TLR4 (PubMed:24380872). Binding to bacterial LPS leads to homodimerization (PubMed:20133493, PubMed:24380872, PubMed:22532668). Interacts with LY96 via the extracellular domain (PubMed:17803912, PubMed:22532668). Interacts with MYD88 (via the TIR domain). Interacts with TICAM2 and TIRAP (PubMed:24380872). Interacts with NOX4 (By similarity). Interacts with CNPY3 and HSP90B1; this interaction is required for proper folding in the endoplasmic reticulum (PubMed:18780723, PubMed:20865800). Interacts with MAP3K21; this interaction leads to negative regulation of TLR4 signaling (By similarity). Interacts with CD36, following CD36 stimulation by oxLDL or amyloid-beta 42, and forms a heterodimer with TLR6. The trimeric complex is internalized and triggers inflammatory response. LYN kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation (By similarity). Interacts with TICAM1 in response to LPS in a WDFY1-dependent manner (PubMed:25736436). Interacts with WDFY1 in response to LPS (PubMed:25736436). Interacts with SMPDL3B (PubMed:26095358). Interacts with CEACAM1; upon lipopolysaccharide stimulation, forms a complex including TLR4 and the phosphorylated form of SYK and CEACAM1, which in turn, recruits PTPN6 that dephosphorylates SYK, reducing the production of reactive oxygen species (ROS) and lysosome disruption, which in turn, reduces the activity of the inflammasome (PubMed:22496641). Interacts with RFTN1; the interaction occurs in response to lipopolysaccharide stimulation (By similarity).By similarity9 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
204224, 23 interactors

Database of interacting proteins

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DIPi
DIP-38573N

Protein interaction database and analysis system

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IntActi
Q9QUK6, 14 interactors

STRING: functional protein association networks

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STRINGi
10090.ENSMUSP00000045770

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
Q9QUK6

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1835
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2Z64X-ray2.84A27-625[»]
3VQ1X-ray2.70A/B22-627[»]
3VQ2X-ray2.48A/B22-627[»]
5IJBX-ray2.91A/B26-544[»]
5IJCX-ray2.57A/B26-544[»]
5IJDX-ray2.70A/B26-544[»]

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
Q9QUK6

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
Q9QUK6

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
Q9QUK6

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section indicates the positions and types of repeated sequence motifs or repeated domains within the protein.<p><a href='/help/repeat' target='_top'>More...</a></p>Repeati54 – 75LRR 1Add BLAST22
Repeati78 – 99LRR 2Add BLAST22
Repeati102 – 123LRR 3Add BLAST22
Repeati126 – 147LRR 4Add BLAST22
Repeati150 – 171LRR 5Add BLAST22
Repeati175 – 198LRR 6Add BLAST24
Repeati204 – 224LRR 7Add BLAST21
Repeati226 – 247LRR 8Add BLAST22
Repeati248 – 269LRR 9Add BLAST22
Repeati329 – 349LRR 10Add BLAST21
Repeati350 – 370LRR 11Add BLAST21
Repeati372 – 392LRR 12Add BLAST21
Repeati398 – 420LRR 13Add BLAST23
Repeati421 – 442LRR 14Add BLAST22
Repeati446 – 467LRR 15Add BLAST22
Repeati470 – 490LRR 16Add BLAST21
Repeati495 – 516LRR 17Add BLAST22
Repeati519 – 540LRR 18Add BLAST22
Repeati543 – 564LRR 19Add BLAST22
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini576 – 627LRRCTAdd BLAST52
Domaini670 – 816TIRPROSITE-ProRule annotationAdd BLAST147

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The TIR domain mediates interaction with NOX4.By similarity

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the Toll-like receptor family.Curated

Keywords - Domaini

Leucine-rich repeat, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG4641 Eukaryota
COG4886 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000160778

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000037951

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG018823

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
Q9QUK6

KEGG Orthology (KO)

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KOi
K10160

Identification of Orthologs from Complete Genome Data

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OMAi
FHLMLLA

Database of Orthologous Groups

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OrthoDBi
282372at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
Q9QUK6

TreeFam database of animal gene trees

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TreeFami
TF351113

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
3.40.50.10140, 1 hit
3.80.10.10, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR000483 Cys-rich_flank_reg_C
IPR001611 Leu-rich_rpt
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
IPR000157 TIR_dom
IPR027168 TLR4
IPR035897 Toll_tir_struct_dom_sf

The PANTHER Classification System

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PANTHERi
PTHR44568 PTHR44568, 1 hit

Pfam protein domain database

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Pfami
View protein in Pfam
PF13855 LRR_8, 2 hits
PF01582 TIR, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00369 LRR_TYP, 8 hits
SM00082 LRRCT, 1 hit
SM00255 TIR, 1 hit

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF52200 SSF52200, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS50104 TIR, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

Q9QUK6-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MMPPWLLART LIMALFFSCL TPGSLNPCIE VVPNITYQCM DQKLSKVPDD
60 70 80 90 100
IPSSTKNIDL SFNPLKILKS YSFSNFSELQ WLDLSRCEIE TIEDKAWHGL
110 120 130 140 150
HHLSNLILTG NPIQSFSPGS FSGLTSLENL VAVETKLASL ESFPIGQLIT
160 170 180 190 200
LKKLNVAHNF IHSCKLPAYF SNLTNLVHVD LSYNYIQTIT VNDLQFLREN
210 220 230 240 250
PQVNLSLDMS LNPIDFIQDQ AFQGIKLHEL TLRGNFNSSN IMKTCLQNLA
260 270 280 290 300
GLHVHRLILG EFKDERNLEI FEPSIMEGLC DVTIDEFRLT YTNDFSDDIV
310 320 330 340 350
KFHCLANVSA MSLAGVSIKY LEDVPKHFKW QSLSIIRCQL KQFPTLDLPF
360 370 380 390 400
LKSLTLTMNK GSISFKKVAL PSLSYLDLSR NALSFSGCCS YSDLGTNSLR
410 420 430 440 450
HLDLSFNGAI IMSANFMGLE ELQHLDFQHS TLKRVTEFSA FLSLEKLLYL
460 470 480 490 500
DISYTNTKID FDGIFLGLTS LNTLKMAGNS FKDNTLSNVF ANTTNLTFLD
510 520 530 540 550
LSKCQLEQIS WGVFDTLHRL QLLNMSHNNL LFLDSSHYNQ LYSLSTLDCS
560 570 580 590 600
FNRIETSKGI LQHFPKSLAF FNLTNNSVAC ICEHQKFLQW VKEQKQFLVN
610 620 630 640 650
VEQMTCATPV EMNTSLVLDF NNSTCYMYKT IISVSVVSVI VVSTVAFLIY
660 670 680 690 700
HFYFHLILIA GCKKYSRGES IYDAFVIYSS QNEDWVRNEL VKNLEEGVPR
710 720 730 740 750
FHLCLHYRDF IPGVAIAANI IQEGFHKSRK VIVVVSRHFI QSRWCIFEYE
760 770 780 790 800
IAQTWQFLSS RSGIIFIVLE KVEKSLLRQQ VELYRLLSRN TYLEWEDNPL
810 820 830
GRHIFWRRLK NALLDGKASN PEQTAEEEQE TATWT
Length:835
Mass (Da):95,519
Last modified:May 1, 2000 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i9C83B59F9A220C17
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A2BHU8A2BHU8_MOUSE
Toll-like receptor 4
Tlr4 RP24-209H15.1-004
154Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti87 – 154CEIET…TLKKL → EMNTESKSSEAHALALSHIL SPCQPSRRKLRVKLGSLSYQ RAEEGVRSSEIGYSCLHVDT RHDINAVD (PubMed:16141072).CuratedAdd BLAST68

<p>This subsection of the ‘Sequence’ section provides information on polymorphic variants. If the variant is associated with a disease state, the description of the latter can be found in the <a href="http://www.uniprot.org/manual/involvement_in_disease">'Involvement in disease'</a> subsection.<p><a href='/help/polymorphism' target='_top'>More...</a></p>Polymorphismi

Interstrain analyzes reveals that TLR4 is a polymorphic protein and that the extracellular domain is far more variable than the cytoplasmic domain, which is variable at the C-terminal.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural varianti94D → N in strain: KK/HLJ. 1 Publication1
Natural varianti209M → I in strain: A/J, BALB/cJ, P/J, SODL/EI, SEA/GNJ, NZW/LACJ and VM/DK. 1 Publication1
Natural varianti219D → G in strain: SEA/GNJ. 1 Publication1
Natural varianti254V → I in strain: A/J, BALB/cJ and SEA/GNJ. 1 Publication1
Natural varianti423Q → L in strain: SEA/GNJ. 1 Publication1
Natural varianti477A → S in strain: P/J. 1 Publication1
Natural varianti516T → A in strain: LP/J. 1 Publication1
Natural varianti593E → D in strain: A/J, BALB/cJ, P/J, SODL/EI, SEA/GNJ, NZW/LACJ and VM/DK. 1 Publication1
Natural varianti600N → I in strain: KK/HLJ. 1 Publication1
Natural varianti607A → V in strain: P/J. 1 Publication1
Natural varianti637V → I in strain: P/J. 1 Publication1
Natural varianti712P → H in Lps-tolerant mice. 2 Publications1
Natural varianti761R → H in strain: A/J, BALB/cJ, SODL/EI, SEA/GNJ, NZW/LACJ and VM/DK. 1 Publication1
Natural varianti811N → K in strain: P/J. 1 Publication1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

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DDBJi
Links Updated
AF095353 mRNA Translation: AAC99411.1
AF110133 mRNA Translation: AAD29272.1
AF185285 mRNA Translation: AAF04278.1
AF177767 Genomic DNA Translation: AAF05317.1
AK014533 mRNA No translation available.

The Consensus CDS (CCDS) project

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CCDSi
CCDS18271.1

NCBI Reference Sequences

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RefSeqi
NP_067272.1, NM_021297.3

UniGene gene-oriented nucleotide sequence clusters

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UniGenei
Mm.38049

Genome annotation databases

Ensembl eukaryotic genome annotation project

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Ensembli
ENSMUST00000048096; ENSMUSP00000045770; ENSMUSG00000039005

Database of genes from NCBI RefSeq genomes

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GeneIDi
21898

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
mmu:21898

UCSC genome browser

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UCSCi
uc008thv.1 mouse

Keywords - Coding sequence diversityi

Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF095353 mRNA Translation: AAC99411.1
AF110133 mRNA Translation: AAD29272.1
AF185285 mRNA Translation: AAF04278.1
AF177767 Genomic DNA Translation: AAF05317.1
AK014533 mRNA No translation available.
CCDSiCCDS18271.1
RefSeqiNP_067272.1, NM_021297.3
UniGeneiMm.38049

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2Z64X-ray2.84A27-625[»]
3VQ1X-ray2.70A/B22-627[»]
3VQ2X-ray2.48A/B22-627[»]
5IJBX-ray2.91A/B26-544[»]
5IJCX-ray2.57A/B26-544[»]
5IJDX-ray2.70A/B26-544[»]
ProteinModelPortaliQ9QUK6
SMRiQ9QUK6
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204224, 23 interactors
DIPiDIP-38573N
IntActiQ9QUK6, 14 interactors
STRINGi10090.ENSMUSP00000045770

Chemistry databases

BindingDBiQ9QUK6
ChEMBLiCHEMBL1795167

PTM databases

iPTMnetiQ9QUK6
PhosphoSitePlusiQ9QUK6

Proteomic databases

MaxQBiQ9QUK6
PaxDbiQ9QUK6
PRIDEiQ9QUK6

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000048096; ENSMUSP00000045770; ENSMUSG00000039005
GeneIDi21898
KEGGimmu:21898
UCSCiuc008thv.1 mouse

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
7099
MGIiMGI:96824 Tlr4

Phylogenomic databases

eggNOGiKOG4641 Eukaryota
COG4886 LUCA
GeneTreeiENSGT00940000160778
HOGENOMiHOG000037951
HOVERGENiHBG018823
InParanoidiQ9QUK6
KOiK10160
OMAiFHLMLLA
OrthoDBi282372at2759
PhylomeDBiQ9QUK6
TreeFamiTF351113

Enzyme and pathway databases

ReactomeiR-MMU-140534 Caspase activation via Death Receptors in the presence of ligand
R-MMU-166016 Toll Like Receptor 4 (TLR4) Cascade
R-MMU-166166 MyD88-independent TLR4 cascade
R-MMU-2562578 TRIF-mediated programmed cell death
R-MMU-5686938 Regulation of TLR by endogenous ligand
R-MMU-936964 Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
R-MMU-937041 IKK complex recruitment mediated by RIP1
R-MMU-937072 TRAF6-mediated induction of TAK1 complex within TLR4 complex

Miscellaneous databases

EvolutionaryTraceiQ9QUK6

Protein Ontology

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PROi
PR:Q9QUK6

The Stanford Online Universal Resource for Clones and ESTs

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SOURCEi
Search...

Gene expression databases

BgeeiENSMUSG00000039005 Expressed in 161 organ(s), highest expression level in aortic valve
CleanExiMM_TLR4
ExpressionAtlasiQ9QUK6 baseline and differential
GenevisibleiQ9QUK6 MM

Family and domain databases

Gene3Di3.40.50.10140, 1 hit
3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR000483 Cys-rich_flank_reg_C
IPR001611 Leu-rich_rpt
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
IPR000157 TIR_dom
IPR027168 TLR4
IPR035897 Toll_tir_struct_dom_sf
PANTHERiPTHR44568 PTHR44568, 1 hit
PfamiView protein in Pfam
PF13855 LRR_8, 2 hits
PF01582 TIR, 1 hit
SMARTiView protein in SMART
SM00369 LRR_TYP, 8 hits
SM00082 LRRCT, 1 hit
SM00255 TIR, 1 hit
SUPFAMiSSF52200 SSF52200, 1 hit
PROSITEiView protein in PROSITE
PS50104 TIR, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiTLR4_MOUSE
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q9QUK6
Secondary accession number(s): Q9D691, Q9QZF5, Q9Z203
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 11, 2002
Last sequence update: May 1, 2000
Last modified: January 16, 2019
This is version 172 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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